What is New in the Most Recent Guidelines for the Management of Dyslipidemias of the European Society of Cardiology and the European Atherosclerosis Society?

Posljednje smjernice o liječenju dislipidemija Europskoga kardiološkog društva i Europskoga društva za aterosklerozu došle su nakon dvaju velikih istraživanja koja su dokazala učinkovitost inhibitora proprotein konvertaze subtilizin/keksin tipa 9 (PCSK9i), ali i ključnu činjenicu da svako dodatno sniženje LDL kolesterola smanjuje povišeni kardiovaskularni rizik, odnosno da ne postoji preniska ciljna koncentracija LDL kolesterola u krvi. Navedeno se odrazilo na preporuku o mnogo nižim ciljnim vrijednostima LDL kolesterola, napose za osobe s visokim i vrlo visokim kardiovaskularnim rizikom, zbog čega je prepoznata potreba za kombiniranjem statina s drugim hipolipemicima, prije svega ezetimiba, a zatim i PCSK9i. U liječenju osoba s visokim rizikom s hipertrigliceridemijom usprkos primjeni statina preporučene su omega-3 masne kiseline. Došlo je do nekih preinaka u kategorizaciji kardiovaskularnog rizika, prije svega u osoba sa šećernom bolešću i s obiteljskom hiperkolesterolemijom, a pridana je i veća važnost određivanju apolipoproteina B i lipoproteina(a) u preciznijoj procjeni kardiovaskularnog rizika. Sada nam preostaje uložiti znatan trud u to da navedene preporuke implementiramo u svakodnevnu kliničku praksu i tako dodatno smanjimo teret zbog kardiovaskularnih bolesti u populaciji.The most recent Guidelines for the management of dyslipidemias of the European Society of Cardiology and the European Atherosclerosis Society arrived after two major studies that demonstrated the efficiency of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), as well as the key fact that every additional reduction of LDL cholesterol reduces increased cardiovascular risk, i.e. that there is no lower limit of target blood concentration of LDL cholesterol. The latter was reflected in the recommendation of significantly lower target values of LDL cholesterol, especially for people with high and very high cardiovascular risk, resulting in the recognition of the need to combine statins with other hypolipemic agents, primarily ezetimibe followed by PCSK9i. Omega-3 fatty acids are recommended for the treatment of high-risk patients with hypertriglyceridemia despite statin treatment. Some modifications were made to cardiovascular risk categories, primarily for patients with diabetes mellitus and familial hypercholesterolemia, and more importance has been assigned to determining apolipoprotein B and lipoprotein(a) for more precise assessment of cardiovascular risk. We are now tasked with investing significant efforts into implementing these recommendations in our daily clinical practice in order to further reduce the population burden of cardiovascular diseases

Takotsubo cardiomyopathy (broken heart syndrome)

Takotsubo cardiomyopathy (TC), also known as stress cardiomyopathy is an uncommon disease characterized by acute left ventricle (LV) failure that mimics acute coronary syndrome (ACS) but lacking evidence of obstructive coronary artery disease. It is usually precipitated by severe emotional or physical stress although its’ pathophysiology is not yet fully known. Most patients are women past the age of 50. In-hospital mortality is 3-4%

Intestinal injury due to sodium polystyrene sulfonate (SPS) treatment in a heart transplant patient

Sodium polystyrene sulphonate (SPS) is a cation exchange resin widely used to treat hyperkalemia in patients with renal failure. Although infrequent, one of its most severe side effects is a gastrointestinal mucosal injury that is most commonly located in the colon. The injury can range from mild superficial injury to wall necrosis and perforation. The causative mechanisms are still unclear. The risk factors include end- stage renal disease, hemodynamic instability, solid organ transplantation, postoperative status and gastrointestinal motility disorders, including opioid usage. CASE REPORT One month after a successful heart transplantation the patient presented with sudden hematochezia and hemorrhagic shock. Emergency laparotomy, right hemicolectomy, and end ileostomy were performed. Histopathological analysis of the resected colon revealed mucosal injury with the presence of crystals of Kayexalate in the necrotic regions. We later found out that several days before this event, the patient received SPS for the treatment of hyperkalemia owing to mild deterioration of chronic kidney disease. The patient fully recovered and was discharged from the hospital. CONCLUSION Acute lower gastointestinal bleeding has many causes, but SPS-related mucosal injury and intestinal perforation is unusual. Since our patient had several predisposing factors for this serious side effect it is important to use SPS only when necessary, especially in the postoperative patients and in those with gastrointestinal motility disorders. Although similar cases of intestinal injury after SPS therapy in solid organ transplant patients have alredy been reported this is, to our knowledge, the first reported case in a patient who underwent a heart transplantation

ASPIRIN RESISTANCE

Iako je acetilsalicilna kiselina u farmakoterapiji prisutna već više od 100 godina, i dalje je kamen temeljac primarne i sekundarne prevencije u kardiovaskularnih bolesnika. Unatoč nedvojbenoj koristi od njezine uporabe, u jednog dijela liječenih ipak će doći do nepovoljnih aterotrombotskih manifestacija poput tromboze u stentu, infarkta miokarda, moždanog udara ili kardiovaskularne smrti. Posljednjih godina sve je više znanstvenog interesa usmjereno na ispitivanje povezanosti ovih događaja s laboratorijskim dokazom slabijeg antitrombocitnog učinka acetilsalicilne kiseline, što je i dovelo do nastanka koncepta tzv. aspirinske rezistencije. Osim nedostatka zajedničke definicije ove pojave, važan je problem u njezinu istraživanju i velik broj različitih te slabo standardiziranih laboratorijskih metoda. Unatoč velikom broju objavljenih studija koje govore u prilog njezinoj kliničkoj važnosti, još ne postoje preporuke struke o potrebi rutinskog testiranja bolesnika na aspirinsku rezistenciju, kao ni prilagođavanja doza ili vrste antiagregacijskih lijekova u slučaju pozitivnog nalaza.Although present in pharmacotherapy for more than 100 years, aspirin still represents a cornerstone in the primary and secondary prevention of cardiovascular patients. Despite undoubtful benefit, a certain proportion of patients treated with aspirin develops adverse atherothrombotic events like stent thrombosis, myocardial infarction, stroke and cardiovascular death. In recent years, there is a growing scientific interest concerning the relationship of suboptimal antiplatelet response to aspirin and cardiovascular prognosis that has led to the concept of »aspirin resistance«. Besides the absence of uniform definition of aspirin resistance, an important issue in these studies are numerous and poorly standardized laboratory methods that are used in its detection. Despite an increasing number of reports that favour its clinical significance, there are still no expert recommendations for routine assessment of platelet aggregation as well as for modification of antiplatelet doses or regimens in the case of established aspirin resistance

Heart transplantation in patient with diabetes- related microvacular and macrovascular complications

Cardiac transplantation is a method of choice in the treatment of patients with end-stage heart failure (HF) whose life expectancy, despite the optimal medical therapy is less than one year. Number of patiences with diabetes are increasing at alarming rates. Some studies have shown an increased risk of post-transplant infection, transplanted organ rejection, renal failure and mortality in diabetic recipients. A 38-year-old African American male patient with end-stage ischemic biventricular cardiomyopathy and diabetes mellitus type 1 with moderate chronic renal failure, was transplanted in August 2014. A few days following the transplantation his renal function continued to deteriorate and chronic haemodialysis was initiated. During the next four years, the regular heart biopsies showed no signs of acute cellular or humoral rejection and echocardiography showed normal graft function. In February 2018 the patient was listed for kidney transplantation. In April 2018 the patient presented with septic shock. Due to the severe eosinophilia combined with culture-negative severe sepsis, complete viral and parasitic serology was performed. All tests came back negative. Bone marrow aspiration showed only eosinophilia. Due to the sepsis of unknown origin, the patient was treated with broad-spectrum antibiotic therapy without an effective response to applied therapy. Despite of the all intensive care treatment, the patient died. Autopsy showed a pancarditis possibly caused by Trypanosoma cruzi or Toxoplasma gondii. In conclusion, cardiac transplantation can be performed in diabetic patients with chronic renal failure, but with significantly increased risk for further renal deterioration and even the need for chronic haemodialysis

Post-transplant lymphoproliferative disorder after heart transplantation

Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoid neoplasms associated with immunosuppression following solid organ transplantation or allogeneic hematopoietic stem cell transplantation. Mismatch for cytomegalovirus (CMV), such as when a seronegative recipient receives an organ from a seropositive donor, was shown to be associated with a seven-fold increase in PTLD. A 20-year-old male patient was admitted to the hospital due to back and abdominal pain. He had underwent a heart transplant 6 years ago due to postmyocarditic dilated cardiomyopathy and soon after the transplant, he had developed CMV pneumonitis. At examination, abdominal ultrasound showed multiple lesions of the liver, and patohystology of the lesion biopsy revealed PTLD, i.e. Non-Hodgkin’s diffuse large B cell lymphoma, for which the patient received 8 cycles of chemotherapy (R-CHOP protocol). Nine months after the first dose, the patient was admitted to the hospital due to simptoms of heart failure (NYHA IV) and echocardiography revealed significantly reduced cardiac function (LVEF 25%). Graft rejection was excluded with heart biopsy and it was concluded the etiology of heart failure was anthracycline (Doxorubicin) toxicity. Given the severity of the patient’s condition, he was again listed for heart transplant, and ultimately, retransplanted. Eight years after the retransplant, the patient is in excellent overall condition. Heart transplant patients have about a 1- 6% risk to develop the PTLD. The incidence of chronic Doxorubicin cardiotoxicity is about 1.7%. This patient had developed both, but, fortunately, with timely and right therapy the outcome can be successful

NEFROPATIJA UZROKOVANA BK VIRUSOM U BOLESNIKA S TRANSPLANTIRANIM SRCEM: PRVI DOKUMENTIRANI SLUČAJ U HRVATSKOJ

As outcomes following heart transplantation have improved significantly over the last years, chronic kidney disease has become an increasingly prevalent complication in this population. Polyomavirus-associated nephropathy (PVAN) of native kidneys has also been recognized increasingly as a cause of kidney failure. We report the first case of PVAN occurring in the native kidneys of a solid-organ transplant recipient in Croatia as the eighth case described in the literature worldwide. A 65-year-old female with dilatative cardiomyopathy and good kidney function had a heart transplanted in 2012. Initial immunosuppressive therapy consisted of antithymocyte immunoglobulin with cyclosporine, mycophenolate mofetil and corticosteroids. Soon after transplantation, her kidney function began to fail progressively. Biopsy of the native kidneys revealed PVAN, and everolimus was introduced in immunosuppressive therapy. Nevertheless, her renal dysfunction progressed and she is now being evaluated for cadaveric kidney transplantation. PVAN should be considered in the differential diagnosis of new-onset renal failure following non-kidney solid organ transplantation. Early diagnosis is essential for prevention of irreversible renal damage.Unazad nekoliko godina sa značajnim poboljšanjem preživljenja bolesnika s transplantiranim srcem kronično zatajenje bubrega postalo je sve češća komplikacija u toj populaciji. Nefropatija uzrokovana poliomavirusom (PVAN) nativnih bubrega također se sve češće prepoznaje kao uzrok zatajenja bubrega. Prikazujemo prvi slučaj PVAN nativnih bubrega kod primatelja transplantata solidnog organa u Hrvatskoj i osmi takav slučaj dosad opisan u literaturi. Bolesnici u dobi od 65 godina s dilatativnom kardiomiopatijom i dobrom bubrežnom funkcijom je 2012. godine transplantirano srce. Inicijalna imunosupresivna terapija sastojala se od antitimocitnog imunoglobulina s ciklosporinom, mikofenolat mofetilom i kortikosteroidima. Ubrzo nakon transplantacije dolazi do zatajenja bubrega. Biopsijom nativnih bubrega postavljena je dijagnoza PVAN, a u imunosupresivnu terapiju je uveden everolimus. Usprkos tome dolazi do daljnjeg napredovanja zatajenja bubrega i bolesnica je trenutno u pripremi za kadaveričnu transplantaciju bubrega. PVAN treba razmotriti u diferencijalnoj dijagnozi novonastalog zatajenja bubrega nakon transplantacije solidnih organa. Rana dijagnoza PVAN je bitna u sprječavanju razvoja ireverzibilnog bubrežnog zatajenja

Heart transplantation in patient with diabetes- related microvacular and macrovascular complications

Cardiac transplantation is a method of choice in the treatment of patients with end-stage heart failure (HF) whose life expectancy, despite the optimal medical therapy is less than one year. Number of patiences with diabetes are increasing at alarming rates. Some studies have shown an increased risk of post-transplant infection, transplanted organ rejection, renal failure and mortality in diabetic recipients. A 38-year-old African American male patient with end-stage ischemic biventricular cardiomyopathy and diabetes mellitus type 1 with moderate chronic renal failure, was transplanted in August 2014. A few days following the transplantation his renal function continued to deteriorate and chronic haemodialysis was initiated. During the next four years, the regular heart biopsies showed no signs of acute cellular or humoral rejection and echocardiography showed normal graft function. In February 2018 the patient was listed for kidney transplantation. In April 2018 the patient presented with septic shock. Due to the severe eosinophilia combined with culture-negative severe sepsis, complete viral and parasitic serology was performed. All tests came back negative. Bone marrow aspiration showed only eosinophilia. Due to the sepsis of unknown origin, the patient was treated with broad-spectrum antibiotic therapy without an effective response to applied therapy. Despite of the all intensive care treatment, the patient died. Autopsy showed a pancarditis possibly caused by Trypanosoma cruzi or Toxoplasma gondii. In conclusion, cardiac transplantation can be performed in diabetic patients with chronic renal failure, but with significantly increased risk for further renal deterioration and even the need for chronic haemodialysis